10 - Neurotransmitter Release Flashcards
What are two types of synapses?
Electrical synapse
Chemical synapse
Why is there a delay in electrical synapses?
There isn’t. Electric coupling has no delay
What contributes to delay in chemical synapses (7)
- Depolarization of terminal
- Opening of Ca2+ channels
- Ca2+ binding to release site
- Vesicle fusion with plasma membrane (exocytosis)
- Diffusion across cleft
- Binding of agonist to receptor
- Opening of postsynaptic channel
How do fast chemical synapses operate?
- Presynaptic depolarization
- Opening of voltage-gated calcium channels
- Presynaptic calcium entry
- Triggering of vesicle exocytosis by calcium
- Release of transmitter
- Activation of postsynaptic receptor
Steps 3-6 are very fast (<1ms at body temp)
Ca2+ domains are important in ____ (neurotransmitter)
Ca2+ domains are important in regulating release (neurotransmitter)
What is the theory behind photolysis of “caged” calcium?
- discovered by Delaney and Zucker
- Inject nitrophen = UV labile calcium buffer in presynaptic terminal
- to see if [Ca2+] is raised enough for release
- Photorelease of Ca2+ in presynaptic terminal mimics timecourse of AP - evoked transmitter release (EPSP)
Describe the Quantal Release Hypothesis from the 1950’s
- Molecules of transmitter are released from synapses in packages (each with approx the same amount of transmitter) Package = quantum
- Nature of “package” is undefined at this point
- Release probability for these packages will increase briefly when the presynaptic nerve is stimulated
Individual package of transmitter
Quantum
Number of quanta released after each stimulus (in units of 0, 1, 2, 3,etc)
Quantal content
What is quantal size
Related to number of transmitter molecules in each quantum
Average number of quanta released per stimulus (w/ repeated stimuli)
Mean Quantal Content (m)
What is Miniature (spontaneous) synaptic potential?
- Proposed by Fatt and Katz (1952)
- Applied prostigmine (Cholinesterase inhibitor) - C
- Increases stimulated transmitter release
- Quantal synaptic records (= no APs)
- frequency unchanged but amplitude larger
- Therefore synaptic quanta are released spontaneously
In an extracellular sol’n with high [Mg2+] and low [Ca2+] what happens?
- Probability of evoked release is lowered
- Stimuli often triggered no release at all (=Failure)
evoked endplate potentials fluctuated approx with the amplitude of miniature potentials
** IMAGE from slide 16** Boyd and Martin compared amplitude distributions in 1956 to what result?
Spontaneous potentials, epp’s had same “quantal” (ie discrete) distribution
Note that epp distribution peaks are centered at multiples of the single spontaneous potential peak
What is Poisson distribution? When is it applicable to data?
- Applicable to data when “mean quantal content” (m) is small (ie evoked synaptic responses are rare)
- Model needs to account for the variance in quantal size, specifically:
- Occurrence of clear failures
- Area under each successive Gaussian curve
*Poisson Distribution
*
How do you calculate the fraction of responses containing X quanta?
Fraction of responses containing X quanta = (mx / x!) e-m
m = mean amplitude of evoked potential divided by mean amplitude of miniature potential
How to use method of failures to calculate m (mean quantal content)
- Failures = 0th quantum
- When X=0
- both m0 and 0! = 1
- Fraction of failures = e-m
- Therefore m=ln(1/fraction of failures)
Are quantal release and vesicular release equivalent?
No
What is freeze fracture analysis of presynaptic membranes?
Apparatus for quick freezing and nerve stimulation
Number of pits increased with ~5ms delay after nerve stimulation
Mast cells with large granules are stimulated by ____
Mast cells with large granules are stimulated by GTP-g-S
Transmitter release requires 3 things:
- Localized Ca2+ influx (presynaptic depolarization, Ca++ domains)
- Ca++ triggering of fusion (v.v. fast)
- Vesicle fusion (v. fast)
Neurotransmitter release occurs in discrete packages called ____
Neurotransmitter release occurs in discrete packages called quanta
____of neurotransmitter release can be modelled and predicted
Behaviour of neurotransmitter release can be modeled and predicted
____ result from release of contents of a single vesicle
Quanta (electrical) result from release of contents of a single vesicle (chemical)
